MTHFR C677T polymorphism and risk of HCC in patients with liver cirrhosis: role of male gender and alcohol consumption.
BACKGROUND
A single nucleotide polymorphism (SNP) C677T in the methylenetetrahydrofolate reductase (MTHFR) gene has been identified. The TT or CT genotypes show a marked reduction of the enzyme activity; this causes higher homocysteine levels and alterations of folate metabolism. Folate metabolism is essential for DNA synthesis and methylation, crucial steps in carcinogenesis. In this paper, we investigated whether the MTHFR C677T SNP could influence the occurrence of hepatocellular carcinoma (HCC) in a cohort of patients transplanted for end stage liver disease of different etiologies.


METHODS
Two hundred and twelve consecutive patients who underwent liver transplantation for end stage liver disease due to hepatitis B or C, alcoholic liver disease, and other causes were studied. Two hundred and thirty-six blood donors served as controls. Focal hepatic lesions were searched in the sectioned explanted livers. The presence of the MTHFR C677T SNP was determined via polymerase chain reaction amplification.


RESULTS
Among the 65 patients with HCC, 22 had the CC genotype, 30 the CT, and 13 the TT genotype. Only in patients with alcoholic liver disease was a significant association detected between the TT genotype and the presence of liver cancer (6/17 vs. 5/46, p < 0.05). At stepwise logistic regression analysis the independent selected predictors of HCC were found: age at transplantation >55 years (p < 0.001) and the association among male gender, alcoholic liver disease, and MTHFR TT genotype (p = 0.002).


CONCLUSIONS
The present study suggests that male TT carriers with alcoholic cirrhosis bear an increased risk of developing HCC.
Fabris
Carlo
C
Medical Liver Transplantation Unit, DPMSC, University of Udine, Udine, Italy.
Toniutto
Pierluigi
P
Falleti
Edmondo
E
Fontanini
Elisabetta
E
Cussigh
Annarosa
A
Bitetto
Davide
D
Fornasiere
Ezio
E
Fumolo
Elisa
E
Avellini
Claudio
C
Minisini
Rosalba
R
Pirisi
Mario
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000150:complications / Q000235:genetics*; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D012727:Sex Characteristics; D013942:Thymine Nucleotides / Q000235:genetics; D055815:Young Adult
D013942:Thymine Nucleotides; D042965:Methylenetetrahydrofolate Reductase (NADPH2)